Both cellular and humoral immune mechanisms may be involved in the pathogenesis of rheumatoid arthritis (RA). Evaluation of mononuclear cells obtained from synovial fluid has revealed a predominance of lymphocytes although studies have failed to correlate any specific lymphocyte subset with the progression of RA. Recent interest, however, has focused on two immunoregulatory molecules, interleukin-1 (IL-1) and B-cell growth factor (BCGF). Both of these molecules have been detected in the rheumatoid joint and may influence the course of the disease. While monocytes are known to contribute to the production of IL-1, the exact cellular origin of BCGF and IL-1 in the rheumatoid joint remains unknown. Interestingly, a subpopulation of lymphocytes has been shown to be a potent producer of both IL-1 and BCGF. These cells have been morphologically classified as large granular lymphocytes (LGL) and are present in the rheumatoid joint. While LGL are best known for natural killer cell activity, little is known of the biological significance of the non-cytotoxic functions of these cells. Recent studies have documented the ability of subsets of LGL to produce significant quantities of both IL-1 and BCGF. However, the role of LGL with respect to the pathogenesis of RA is unknown. Thus, in this proposal we intend to: 1) phenotypically characterize LGL obtained from the rheumatoid joint utilizing monoclonal antibodies that detect specific cell surface markers and flow cytometry for analysis of stained cells; and, 2) functionally analyze distinct subsets of LGL, purified by flow cytometry, for the production of IL-1 and BCGF.